Abstract: Angiogenesis, the sprouting of new blood vessels from existing vasculature, involves multiple complex biological processes, and it is an essential step for normal hemostasis, tissue healing and regeneration. Excessive or insufficient angiogenesis is linked to a number of human disease conditions. Therefore, development of molecular tools to regulate/control the sprouting of blood vessels is highly desired. Angiogenesis stimulants can ameliorate human disease conditions including limb ischemia, chronic wounds, myocardial infarction, and stroke. On the other hand, angiogenesis inhibitors can ameliorate human diseases such as cancer, macular eye degeneration, synovitis, and psoriasis among others. The current strategies to stimulate or inhibit angiogenesis rely on targeting growth factors, particularly VEGF/FGF and its receptors. These strategies have several limitations: a) poor bioavailability of pro-angiogenic growth factors such as VEGF and FGF2 have remained largely challenging for promoting therapeutic angiogenesis; b) current anti- angiogenic therapies are unable to produce an enduring response, resulting to the upregulation of multiple pro- angiogenic pathways. We hypothesize that manipulation of glycosaminoglycan fine structures would regulate the extent of angiogenesis through activating angiogenic growth factors such as VEGF and FGF2. In this proposal, we aim to develop novel and innovative synthetic tools, which are easily accessible and can be produced in a large scale for clinical use if desired, to facilitate tracking and manipulation of glycosaminoglycan structures with the final goal of regulating angiogenesis. Furthermore, development of synthetic glycan-based tools proposed herein will allow a significant number of biomedical researchers, who may not otherwise conduct glycoscience research, to advance our understanding of glycosaminoglycans in human health and disease through manipulating their structures and functions. !1